Sequence Motifs Specifying Homing and Metastasis to Bone

摘要

Our overall aim was to identify peptide motifs or molecules that may mediate the specific homing of metastatic tumor cells to bone. Our approaches involved the use of random peptide libraries expressed on the surface of filamentous phage as well as an expression cloning strategy using immortalized bone marrow stromal and endothelial cells to detect the binding of Cos-l cells transfected with cDNAs from the bone metastatic MDA-MB-23 I breast cancer cell line. Using both these approaches we have successfully identified two novel CDNAs (A3 and A5) by expression cloning and one novel cDNA of unknown function by a new in vivo targeting strategy. These experimental approaches will lead to the discovery of molecules that may help us uncover the basis mechanisms of bone metastasis by cancer cells which remains today one of fundamental unresolved problems in tumor biology. Furthermore, identification of bone specific homing sequences could enable us to design vectors to be used in gene therapy of genetic diseases effecting bone and/or to block bone metastasis.